Guidelines Summary

Imaging

The following organizations have issued guidelines for the use of imaging in the diagnosis of MS:
[69, 133, 134, 135]

Consortium of Multiple Sclerosis Centers (CMSC)

MAGNIMS (Magnetic Resonance Imaging in MS) Network

European Academy of Neurology (EAN)

Although MRI alone cannot be used to diagnose MS, all four guidelines (MAGNIMS has two) concur that it is the imaging procedure of choice for confirming MS and monitoring disease progression in the brain and spinal cord.

In 2005, the MAGNIMS Network released two separate guidelines for use of MRI in MS. One covers diagnosis of suspected MS and the other covers use of MRI in disease monitoring.

The MAGNIMS guidelines find currently available evidence insufficient to support the use of advanced MRI to establish the initial diagnosis or differential diagnosis of MS in patients with CIS.

Other recommendations include the following:

Spinal cord MRI should always be performed in patients with spinal cord symptoms at disease onset

Spinal cord MRI should be performed when brain MRI results are inconclusive, and for all patients with brain MRI suggestive for RIS

The MAGNIMS guidelines recommend more frequent follow-up than the CMSC guidelines, as follows:

3-6 months after baseline brain scan for patients with RIS or CIS and abnormal MRI

If the second brain scan is inconclusive, a third can be done 6-12 months later

Follow-up spinal cord MRI in patients with CIS, to demonstrate dissemination in space (DIS) and dissemination in time (DIT), has limited value and should not be done routinely

The recommendation for monitoring of patients with established diagnosis of MS include the following:

T2-weighted and contrast-enhanced T1-weighted brain MRI are the modalities of choice for MS disease monitoring

The use of spinal cord MRI in addition to brain MRI is not recommended for routine monitoring and should be limited to certain clinical situations (eg, unexplained and/or unexpected spinal cord symptoms)

Although assessment of brain volume does not have a role in the diagnosis of MS, it can be a good predictor of long-term disability

Rates of change in brain volume are not recommended as a marker of disease progression in individual patients, owing to the technical, biological and pharmacological factors that can influence the measurement and interpretation of atrophy rate

MRI should be included in drug monitoring to screen for opportunistic infections, unexpected disease activity (including paradoxical reactions), and comorbidities

In patients at high risk of developing opportunistic infections who are switching disease-modifying drugs (DMDs), brain MRI should be performed at the time the current treatment is discontinued and after the new treatment is started

Enhanced pharmacovigilance, including brain MRI every 3–4 months for up to 12 months, is required in patients who switch from natalizumab to other therapeutics (including fingolimod, alemtuzumab, and dimethyl fumarate)

European Academy of Neurology (EAN)

The 2011 guidelines from the European Academy of Neurology (EAN) offer no significant variance with the CMSC and MAGNIMS guidelines.

Disease-modifying therapies

Currently, most disease-modifying agents have been approved for use only in relapsing forms of MS. To address the need for early intervention, the Multiple Sclerosis Coalition developed a consensus document in 2014 to provide support for broader access to U.S. Food and Drug Administration (FDA)-approved MS disease-modifying therapies.
[136]

The guidelines recommend treatment with an FDA-approved disease-modifying agent as soon as possible after any of the following events:

Diagnosis of relapsing MS

First episode of neurologic symptoms with MRI findings consistent with MS, and other possible causes have been ruled out

Diagnosis of secondary-progressive MS (SPMS) but patient continues to have relapses and/or inflammatory changes on MRI

The guidelines further recommend that treatment with any disease-modifying medication should be continued indefinitely, unless any of the following occur:

The patient or healthcare provider determines that the treatment is failing to adequately control the disease

The side effects are intolerable

The patient is unable to follow the recommended treatment regimen

A more appropriate treatment becomes available

Additional recommendations include the following:

Switch from one disease-modifying treatment to another should only occur for medically appropriate reasons

When a medication is not providing adequate benefit, another agent with a different mechanism of action should be considered

Factors affecting choice of treatment are complex and should be addressed collaboratively by the patient and healthcare provider

Access to treatment should not be limited by frequency of relapses, level of disability, or personal characteristics such as age, gender, or ethnicity

Absence of relapses may indicate that the treatment is working and should not be considered a justification for discontinuing the treatment

European Committee for Research and Treatment of Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN)

In 2017, the ECTRIMS and EAN released the first set of guidelines on the use of disease-modifying therapies in multiple sclerosis. The European guidelines cover the treatment of adults with MS or clinically isolated syndrome (CIS), the monitoring of treatment response, the stopping and switching of treatment strategies, and treatment in special situations, such as pregnancy. There are 20 main recommendations.
[148] Those with strong evidence include the following:

Offer interferon or glatiramer acetate to patients with CIS and abnormal MRI findings with lesions suggesting MS who do not fulfill full criteria for MS.

A study comparing the effectiveness and safety of teriflunomide and interferon beta-1a in patients with relapsing multiple sclerosis (TENERE). 4th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC)/Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). June 2, 2012 (ClinicalTrials.gov identifier: NCT00883337).

A multicenter double-blind parallel-group placebo-controlled study of the efficacy and safety of teriflunomide in patients with relapsing multiple sclerosis who are treated with interferon-beta. (ClinicalTrials.gov identifier: NCT01252355).

[Guideline] Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence: A Consensus Paper. The Consortium of Multiple Sclerosis Centers. Available at http://www.mscare.org/?page=dmt. July 2014;

The mechanism of demyelination in multiple sclerosis may be activation of myelin-reactive T cells in the periphery, which then express adhesion molecules, allowing their entry through the blood-brain barrier (BBB). T cells are activated following antigen presentation by antigen-presenting cells such as macrophages and microglia, or B cells. Perivascular T cells can secrete proinflammatory cytokines, including interferon gamma and tumor necrosis factor alpha. Antibodies against myelin also may be generated in the periphery or intrathecally. Ongoing inflammation leads to epitope spread and recruitment of other inflammatory cells (ie, bystander activation). The T cell receptor recognizes antigen in the context of human leukocyte antigen molecule presentation and also requires a second event (ie, co-stimulatory signal via the B7-CD28 pathway, not shown) for T cell activation to occur. Activated microglia may release free radicals, nitric oxide, and proteases that may contribute to tissue damage.

MRI of the head of a 35-year-old man with relapsing-remitting multiple sclerosis. MRI reveals multiple lesions with high T2 signal intensity and one large white matter lesion. These demyelinating lesions may sometimes mimic brain tumors because of the associated edema and inflammation.

MRI of the head of a 35-year-old man with relapsing-remitting multiple sclerosis. This MRI, performed 3 months after the one in the related image, shows a dramatic decrease in the size of lesions.

Demyelination in multiple sclerosis. Luxol fast blue (LFB)/periodic acid-Schiff (PAS) stain confers an intense blue to myelin. Loss of myelin is demonstrated in this chronic plaque. Note that absence of inflammation may be demonstrated at the edge of chronic lesions.

MRI or await a second clinical attack implicating a different CNS site

and

Dissemination in time, demonstrated by MRI or second clinical attack

· Insidious neurologic progression suggestive of MS

One year of disease progression and dissemination in space, demonstrated by 2 of the following:

One or more T2 lesions in brain, in regions characteristic of MS

Two or more T2 focal lesions in spinal cord

Positive CSF

Notes: An attack is defined as a neurologic disturbance of the kind seen in MS. It can be documented by subjective report or by objective observation, but it must last for at least 24 hours. Pseudoattacks and single paroxysmal episodes must be excluded. To be considered separate attacks, at least 30 days must elapse between onset of one event and onset of another event.